Hematology | Chronic 438 teamwork

Color index: Red: Important Gray: notes Blue: extra Editing file | Chronic leukaemia ➔ Heterogeneous group of hematopoietic neoplasms. ➔ It is uncontrolled proliferation and decreased apoptotic activity with variable degrees of differentiation. ➔ Composed of relatively mature cells. ➔ Indolent. (If untreated, the course is in months or years). ➔ Occurs mainly in adults ➔ Types : MPN , MDS , MPN/MDS. Main types of leukemia

Acute Chronic

Lymphoid ALL LPN(CLL)

MPN/MD AML Myeloid S (CML)

Mixed Acute Biphenotypic

Non Acute | Myeloid proliferative neoplasms (MPN)

➔ Malignant proliferation of myeloid cells (maturing cells) which are mainly , in blood and . ➔ Slow onset and long course. ➔ Occurs mainly in adults.

|Features:

Organomegaly ➔ Pathoma Hypercellular Bone Chronic myeloid leukemia can transform to (mainly AML (⅔ of cases) or ALL (⅓ of cases) since marrow splenomegaly) mutation is in a pluripotent stem cell.

01 02 03 04 05

Cytosis High uric acid Progression to acute (increasing WBCs) leukaemia (Mainly AML) | Chronic myeloid leukemia (CML) Acute ➔ Stem cell MPN. ➔ Predominant proliferation of granulocytic cells. ➔ Consistently associated with the BCR-ABL1 fusion gene, located in the Philadelphia (Ph)

chromosome which results from t(9;22). Chronic ➔ If the mutation happened at () it is AL, otherwise it will be CL especially .

|Pathogenesis:

04 03 02 Uncontrolled 02 proliferation 01 Activation of signal Increase Tyrosine transduction pathways BCR-ABL1 Kinase t(9;22) happened (NAP)score: | Clinical presentation of CML Cytochemical stain that estimate the amount of alkaline phosphatase enzyme in neutrophils .

01 02 Asymptomatic Abdominal discomfort presentation(20-40%) due to splenomegaly 03 04 Routine CBC : marked (increase in Splenomegaly (Massive ) | Treatment of CML WBCs )

05 If no response Targeted therapy Common symptoms : Stem cell Tyrosine kinase Fatigue ,weight loss or transplantation inhibitors night sweating Imatinib , Gleevec

Excellent response (5 years overall survival ≥ 90%) | CML phases

Chronic phase: 01 ● Leukocytosis (12-1000×10⁹/L) ● Mainly neutrophils & ● Blasts ≤10% ,Basophils≤ 20% ● Stable course (years)

Accelerated phase: 02 ● Increasing counts ● 10-19% blasts (basophils ≥20%) ● Unstable course (months)

Blastic phase: 03 ● ≥20% blasts = Acute Leukemia ● 80% AML & 20% ALL ● (coarse: Weeks) | Myelodysplastic Syndromes (MDS) Group of myeloid neoplasms characterized by: death happens within the BM ie; ➔ Peripheral cytopenia ( Low HB ± Low WBC & Low PLT ). premature death of RBC, ➔ 01 thrombocytes, granulocytes And Dysplasia (abnormal morphology). . ➔ Ineffective hematopoiesis (hypercellular marrow). just like CML Blood: Pancytopenia ➔ Progression to AML (preleukaemic disease). with dysplasia. ➔ Enhanced apoptosis.

Subtypes Treatment according to: Supportive ± Blast count, degree of BM: Hypercellular chemotherapy. with dysplasia. dysplasia and genetics.

01 02 03

Genetic Abnormalities

Mainly in -5 and -7 ↑ Proliferation + ↑ Apoptosis = Ineffective Hematopoiesis | Differential Diagnosis

CML Leukemoid Cytosis Cytopenia Age Adult Any age

WBC count High High but < 100,000

Mainly myelocytes & Differential Mainly bands segmented

Morphology Hypogranular Toxic MPN MPN/MDS MDS

Splenomegaly + ±

NAP score Low High

BCR/ABL +ve -ve 1- Chronic myelomonocytic leukemia: (monocytosis ,BCR-ABL –ve) . N.B chronic myeloid leukemia was mainly granulocytes “neutrophils” 2-Leukemoid reaction: Leukocytosis due to physiological response Onset Chronic Acute to stress or infection | Chronic Myelomonocytic Leukemia (CMML) Clonal hematopoietic malignancy characterized by:

● Proliferation of monocytes. ● Proliferation of neutrophils. ● Negative for . Course ● Blast must be less than 20%. Treatment Aggressive course (survival rate around Chemotherapy ± Stem 2.5 years). MDS Features Cell Transplant (SCT) Dysplasia & enhanced apoptosis.

MDS/MPN The reason why it’s called by these two diseases:

MPN Features Marked proliferation. Key answers: | Quiz 1-A 2-B 3-B 4- D

1-22 years old male come to ER with splenomegaly; 3- The most important characteristic for CMML examination show increasing in WBCs and high Uric acid. Microscopic results show hypercellular bone A. Basophil proliferation marrow. What’s your diagnosis? B. proliferation C. B proliferation A. MPN D. proliferation B. CML C. MDS 4- The most important characteristic for MDS (from D. CMML dr.notes)

2- CML associated with A. HyperCellular bone marrow B. HypoCellular bone marrow A. BCR-ABL2 fusion gene in Ph chromosome C. Peripheral blood cyropenia which result from t(9;22) D. A & C B. BCR-ABL1 fusion gene in Ph chromosome which result from t(9;22) C. BCR-ABL1 fusion gene in Ph chromosome which result from t(8;14) D. BCR-ABL1 fusion gene in Ph chromosome which result from t(9;21) THANKS | TEAM MEMBERS

● Amirah Alzahrani ● Abdullah Alghamdi ● Deema Almaziad ● Hashem Bassam | TEAM LEADERS ● Jude Alotaibi ● Mashal Abaalkhail ● Njoud Almutairi ● Moath Aljehani ● | Abdulaziz Alghamdi ● Nouf Albraikan Mohammed Alasmari ● Mohammed H.Alshehri ● Noura Almazrou ● Mohammed Alkhamees | Elaf Almusahel ● Razan Alzohaifi ● Mohammed Alshalan ● Rema Almutawa ● Naif Alsolais ● Renad Alhaqbani ● Raed Alojayri ● Renad Almutawa ● Saud Bin Queid = Done by ● Taif Alotaibi ﺿﻠﻌﻲ Editor = ● Wejdan Alnufaie = Note taker

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